International Ionizing Radiation Metrology Applications for Safety in Health

Transcription

1 International Ionizing Radiation Metrology Applications for Safety in Health Lisa R. Karam Chief, Radiation and Biomolecular Physics Division National Institute of Standards and Technology

2 Radioactivity Spontaneous emission of energy and subatomic particles from individual, unstable atomic nuclei Naturally occurring, or artificially produced Number of decays per second (Bq) Natural background ranges up to 10 s of millions of Bq s per kg Uses in health, environmental studies, industry, scientific research Good measurements are crucial to meet safety and regulatory concerns

3 Basics of Ionizing Radiation 1895 Imaging Therapies Resulting consequences

4 Decay Characteristics Primary particle decay modes:, -, + ( positron ) Special case of electron capture Gamma decay usually follows particle emission Daughter Daughter e Daughter o Parent Parent Parent 211 Fr At C 6 14 N e F 9 18 O e Mo 42 99m Tc Tc 43

5 Nuclear Data Key physics to be considered in radionuclide metrology Type of particle/energy Half-life (t 1/2 ) Energy value(s) Emission probabilities Mode of production Some 150+ possibilities

6 Radiation Effects Water DNA Protein Cellular Repair (correct/incorrect) Linear No-Threshold

7 A Matter of Scale Radiation in Health Care Diagnostics Therapy Sanitation mgy Gy kgy 10 Gy 1 m* *your mileage may vary Safety in Health Care Patient, Practitioner, Materials Dose control: enough to do the job Traceability Leads to Confidence in Measurements Measurements Lead to Confidence in Results

8 Neutron Measurements Absorbed dose and dose rate to graphite, tissue, water, other Ambient dose equivalent and rate Emission anisotropy Emission rate Fluence and fluence rate Personal dose equivalent and rate Dosimetry Absorbed dose/rate to air, graphite, tissue, water, other Air kerma area product Air kerma length product Air kerma/rate Ambient dose equivalent/rate Directional dose equivalent/rate Personal dose equivalent/rate, penetrating or superficial Quantities of Interest Radioactivity Activity Activity per unit area, mass, volume Efficiency of contamination monitors Efficiency of gamma-ray spectrometers (versus energy) Efficiency of ionization chambers Emission rate, rate per unit solid angle Surface emission rate, rate per unit area

9 Safety and Efficacy in Ionizing Radiation Applications First do no harm??? Benefit Risk

10 Medical Diagnostics Metrology for Safe Imaging Early detection (avoid false positives) Therapeutic decisions (avoid repetition) Imaging as biomarker Drug development (clinical trials) Therapeutic response Metrology for Image quality Dose control Computed Tomography (CT) scans (60+ Million in the US per year) Mammographic exams (~40 Million in the US per year) ~-1-2 Million CT scans accompanied by PET imaging in the US per year

11 Cancer Screening Measurements and Standards Assure Patient Safety 1992 MQSA Requires instrument calibration Met by manufacturers (4) and FDA Mammographic machine operation Free-air chambers directly realize air-kerma of kv x-ray beams. AAPM TG-61 protocol converts air kerma to absorbed dose. Peak kilovolt (kvp) voltage standard (proper spectral distribution of x rays) for image quality (avoid repeats) Dose standards (air kerma: energy release in unit mass) National standard for mammography dose >12,000 mammography clinics 1 st NIST/BIPM comparison (normalized calibration coefficients) u c = Prof testing for secondary standards labs (two years) Newer technologies (W anode, Ag or Rh filter) New concerns (air kerma, dose, non-invasive kvp) Response of chambers (flat at energy range) Risk of dose errors (need new calibration) NIST reference beams (parameters similar to PTB, enabling manufacturers export)

12 Following Therapeutic Effects Measurements and Standards Assure Confidence PET/CT To assess disease state In treatment planning In clinical trials (drug development) Usefulness depends on consistency (time, space) Persistent image variability Among clinical sites (activity in phantom or patient, conversion of image intensity to activity, protocols for acquisition, reconstruction, analysis) Among scanners Between scans Recognized need for Physical standards/calibration tools for imaging in change measurement Standards for image generation, transmission, etc. Manufacturers (drug, instrumentation), NCI, prof. societies)

13 Metrology for CT How Big is Big, and How Do You Know? Length and contrast standards Tumor definition Tumor size Cheap, portable NIST-designed phantoms Inexpensive, robust, good contrast Reduce need for repeat scans Implementation Dimensional accuracy NIST-traceable Characterization in NIST-standard x-ray beam Wide density range, good contrast Impacts Developing SRMs Publications (evidence of use) Possibilities in clinical trials 3D visualization reconstructed from CT images 5 cm PMMA cylindrical vial (for PET solution) half filled with water air water X-ray transmission images of foam samples The missing piece: Dose

14 Metrological Challenge Traceability of 18 F Despite 2-hour Half-Life Input from stakeholders show needs Traceability for instrument calibration Longer-lived Phantom variety Protocols Ge-68 (t 1/2 271 d) National standard 18 F Primary Standard u c = 0.61 % 18 F Syringe u c = 0.83 % RF = RF =? Calibration for different geometries (syringe, phantoms) Goal: u c < 1 % Issues discovered Traceable 68 Ge mock-syringes, 3 clinical sites (30+ ) Manufacturer-recommended settings for 18 F Comparison with NIST traceable activity value for 18 F Results all 5-6 % too high Status Calibration transferred to NIST Secondary Standard IC (routine future calibrations) 68 Ge Syringe Mock Standard u c = 0.52 % 18 F Phantom 68 Ge Phantom u c = 0.7 % u c = 0.34 % 68 Ge Primary Standard

15 Targeted, bloodless Leverage for other therapies External and Internal Site specific Additive ( fractionation ) Goldilocks Metrology for Mapping Efficacy Protecting the practitioner Radiation Therapy Metrology to Assure Focus

16 Metrology for External Beam Therapy A Workhorse of Cancer Treatment In the clinic About ½ cancer patients (~800 K in US) Targeted (providing focused approaches) Often adjunct to other therapies Controlling impact Fractionation Stereotactic Measurement challenges to safety Variety of rad types (protons, photons, electrons) Dose mapping Dose to normal tissue control Dose to clinicians (radiation protection) Metrological needs Absorbed dose in tissue Confidence in user dosimetry Standards for modern methods (accelerator vs. Co-60)

17 Measurement Traceability for Clinical Accelerator Beams Expanded Uncertainty at k = 2 Patient doses 5 % - maximize cure; minimize complications requires 3 % for the reference beam calibration, thus hospital dosimeter calibration better than 2.5 % > 5 % - investigation initiated > 10 % - incident reported > 20 % - serious incident / accident SI traceability NMI secondary/working standard > 2 % NMI national standard > 1.5 % BIPM standard for comparisons and calibrations > 1 % More direct for clinical beams than Co-60 Ensures traceability to the SI Provides confidence in measurements Supports CMC declarations Satisfies legislation Impacting 5 % to 10 % of patients Snapshot of degrees of equivalence for 60 Co absorbed dose to water from BIPM or RMO comparisons. hospital linear accelerator calibration Beam calibrations between 3 % and 5 % (11 % of results) would benefit immediately from direct calibrations and absorbed dose protocols (13 M doses per year)

18 On-Site Comparisons at NMIs BIPM.RI(I)-K6, Absorbed Dose to Water Requires well-characterized LINAC for dissemination (not available at all NMIs) Participations to date: PTB (Germany), NIST (USA), LNE-LNHB (France), NRC (Canada) BIPM primary standard graphite calorimeter being set up in accelerator beam (BIPM u i = from 6 MV to 20 MV) Future participations: ARPANSA (Australia, autumn 2012), METAS (Switzerland, spring 2013), NPL (UK, autumn 2013) Results given as ratios with a combined standard uncertainty

19 Metrological Infrastructure Meeting Needs for Evolving Technologies Absorbed dose standards Second generation primary standard Clinical accelerator Water calorimetry to directly realize absorbed dose in therapy beams Measurements depend on Exposure times Heat conduction, convection issues Ambient temperature control Agreement within uncertainty of 0.3 % Small field radiotherapies (alanine) Radiation protection Improving dosimetry systems (improved accuracy, stability, energy discrimination) 137 Cs Gamma-ray calibration range Extends range of air kerma values available To be available soon 60 Co Water v Wheatstone bridge Insulation Shutter Lock-in amplifier Pulsed Sensing Thermistors in sealed glass core AAPM TG-51 protocol allows measurement of dose in MV photon beams from radiotherapy linacs

20 Irradiation From Within Measurement Standards to Confine the Field Brachytherapy Concentrates radiation field to organ radioactive seeds Effectiveness of therapy Safety Issues Surrounding normal tissue Maximize dosage to tumor site Measurement Needs Dose distribution within each seed Computation of radiation cloud Difficulties Anisotropy Multiple manufactures Change in construction, materials Achieving traceability Work through SSDLs, manufacturers Transfer to clinic calculation by Sharron Trumpore, Yale- New Haven Hospital Primary air kerma standard realized with WAFAC Typical uncertainties on the order of 2 %

21 Precision for the Radiopharmacy Metrology for Safer Nuclear Medicine Standardization of 223 Ra Bone-seeking nuclear medicine application Treat skeletal metastases, assoc. bone pain In clinical trials (prostate and breast cancer) FDA required NIST standard before initiation of clinical trials in the US CIEMAT/NIST Results agreed with 2πα PC measurements (well within uncertainties; final expanded uncertainty at k=2: 0.49 %) Accounted for potential losses (none observed from adsorption, radon, 215 Po; cocktail stability showed some influence) Large discrepancy remains between alpha/beta measurements and gamma measurements Future plans dose calibrator factors (for clinical users)

22 A Future Without Sources? Electronic Brachytherapy Using miniature x-ray sources Low energy x rays (< 50 kev) Calibration Use of Lamperti free-air chamber Internally compared to other x-ray standards in-house Energy spectrum followed in real-time Monte Carlo simulations Same issues with anisotropy Implementation Evaluation of potential transfer standard (IC) to disseminate to user community (through ADCLs) To be used to calibrate monitoring equipment in therapy clinics Xoft AXXENT TM electronic brachytherapy source in NIST lab

23 Radiation to Assure Patient Safety Medical Device Sterilization 50 % of all medical products are sterilized with gamma rays Include devices and tissues Adequate dose to assure sterility Maintain material integrity NIST traceable, empirically verified protocols for gamma and electron beam dosimetry in device sterilization NIST transfer dosimetry based on alanine films/pellets (EPR) QA for device sterilization, blood irradiations, tissue treatments Assuring traceability Meeting regulatory requirements One day, remote calibrations? E-beam sterilization Alanine films & pellets Lyophilized tissue for transplantations

24 NIST Radiation Metrology and Standards Medical Physics and Health Radiation Physics Theoretical dosimetry Codes and models Measurements in dosimetry Brachytherapy X-ray calibrations Calibrations for external beam Standards for mammography Radionuclide metrology Nuclear medicine Quantitative med imaging (CT, PET) Radionuclide standardization SRMs, Calibrations Providing critical radiation measurement infrastructure for assuring safety in health care

25 Future of Radiation Metrology to Assure Safety in Health Care National intercomparison facility for dose calibrators 3-D dose distribution from Clinac Measurement standards for Hybrid ( hyphenated ) techniques (PET-MRI, etc.) image quality Dose for CT, other methods Patient-based quantitative nuclear medicine imaging Metrology for x-ray-based bone-density measurements (DXA) Support for personalized medicine Leveraging NIST s unique neutral position to objectively address metrological needs for safer and more effective health care

26 Facilities Primary Establishing Radiation Metrology Secondary Expertise Regulations Traceability Working with RMO and NMIs

27 Partners in Metrology Propagating Safety Metrology not done in vacuo User and stakeholder communities Collaborators (manufacture) International partners (trade) SIM MWG 6 Canada, US, Mexico, Brazil, Uruguay, Argentina Measurement traceability CIPM MRA; CCRI Sections I, II and III Comparisons Radiation safety in health care depends on metrology Get the job done Do no harm Provide cleanliness Confidence for patients Protection for practitioners

28 Paris 14 October 1999 The CIPM MRA 40 entities originally, now 87 (plus designated) Mutual recognition of National measurement standards Calibration and measurement certificates Structure RMOs Member States Associates of the CGPM Designated Institutions

29 Origins and Function Growing importance of metrology Enable world trade Overcome technical barriers Recognized foundation for variety of scientific and societal activities Secure technical foundation for wider agreements NMIs of Member States of the Metre Convention or Associate States (economies) of the CGPM Consultative committees focus on metrology in sound, length, mass, electricity/magnetism, time, thermometry, photometry, chemistry, and ionizing radiation (CCRI) Sections I (P. Sharpe), II (L. Karam) and III (D. Thomas)

30 Short, medium, longterm actions Close collaboration with stakeholders Close dialogue with end users Activities through Sections, WGs and Members A Strategy for CCRI Advice and Transparency CCRI Vision: become the undisputed hub for ionizing radiation global metrology

31 Implementing the Strategy Actions in Neutron Metrology Knowledge transfer (promoting neutron metrology, increasing dialogue) Radiation protection (personal dosimeters still an issue) Radiation hardness testing (need for extended range of monoenergetic neutrons esp. >20 MeV; collaborations?) Fusion (standards: identify, develop?) Nuclear data cross sections (is there a coordination role for the CCRI?) Control instrumentation fission reactors (new needs in industry: uniqueness of NIST radiography) Security (PFNA)

32 CIPM MRA Participants in the Americas Country Institute Date Signed Argentina INTI (CNEA designate) 14 Oct 1999 Bolivia* IBMETRO 16 May 2008 Brazil INMETRO (LNMRI/IRD designate) 14 Oct 1999 Canada NRC-INMS 14 Oct 1999 Caribbean Community* Designates in 11 countries 12 Oct 2005 Chile INN 18 Oct 2000 Costa Rica* LACOMET 6 Oct 2004 Cuba (COOMET)* NC (CENTIS and CPHR designate) 18 June 2001 Ecuador* ININ 15 April 2001 Jamaica* BSJ 21 July 2004 Mexico CENAM (ININ designate) 14 Oct 1999 Panama* CENAMEP AIP 16 Sept 2003 Paraguay* INTN 27 Oct 2009 Peru* INDECOPI 17 Nov 2009 USA NIST 14 Oct 1999 Uruguay LATU (MIEM/Lab. Tecnogestión designate) 14 Oct 1999 International Organizations IAEA; IRMM 14 Oct 1999 *Associate of the CGPM

33 SIM Signatory Labs in Ionizing Radiation Metrology Working Group 6 Country Institute Field Argentina CNEA Dosimetry, Radioactivity Brazil LNMRI/IRD Dosimetry, Radioactivity, Neutron measurements Canada NRC-INMS Dosimetry, Radioactivity, Neutron measurements Mexico ININ Dosimetry, Radioactivity, Neutron measurements Uruguay MIEM/Laboratorios Tecnogestión Dosimetry USA NIST Dosimetry, Radioactivity, Neutron measurements

34 Neutron Measurements Absorbed dose and dose rate to graphite, tissue, water, other Ambient dose equivalent and rate Emission anisotropy Emission rate Fluence and fluence rate Personal dose equivalent and rate Dosimetry Absorbed dose/rate to air, graphite, tissue, water, other Air kerma area product Air kerma length product Air kerma/rate Ambient dose equivalent/rate Directional dose equivalent/rate Personal dose equivalent/rate, penetrating or superficial Quantities of Interest Radioactivity Activity Activity per unit area, mass, volume Efficiency of contamination monitors Efficiency of gamma-ray spectrometers (versus energy) Efficiency of ionization chambers Emission rate, rate per unit solid angle Surface emission rate, rate per unit area n 0

35 Calibration and Measurement Capabilities (CMCs) Initially, synonymous with Best Capability Measurement used in accreditation In 2008, BIPM, ILAC and RMOs agreed to a clarified, common, annotated definition: A CMC is a calibration and measurement capability available to customers under normal conditions (a) as published in the BIPM key comparison database (KCDB) of the CIPM MRA; or (b) as described in the laboratory s scope of accreditation granted by a signatory to the ILAC arrangement Where the term NMI is used, it is intended to include Designated Institutes (DIs) within the framework of the CIPM MRA Published CMCs in SIM: 30 in dosimetry, 515 in radioactivity, 10 in neutrons

36 Role of Comparisons Key component of CMCs Guidance on uncertainty expectations Aid in review process Improved metrological rigor Key and supplementary Allows improvements in methods Planning for future comparisons (optimizing resources) Successful participation to support equivalency

37 Comparisons in Dosimetry Supporting Traceability for Diagnostics and Therapies Currently, 43 comparisons in x and gamma rays, and electrons measurements (dosimetry) are listed in the Key Comparison Database (KCDB; Appendix B) Comparisons include SIM, EURAMET, COOMET, APMP, CCRI(I), BIPM Planned, in progress, measurements complete, Draft B, approved/published, equivalence Absorbed dose to water, absorbed dose rate for beta, air kerma (low and med energy, Co-60), personal dose equivalent

38 SIM.RI(I)-K4 Measurement of absorbed dose for Co-60 to water Run in 2002 along with SIM.RI(I)-K1 Three cavity ionization chambers used as transfer instrument Key comparison Series of bilateral comparisons between NRC and participating countries CNEA IAEA ININ LNMRI LSCD NIST* NRC* Participants National Commission of Atomic Energy; Argentina, SIM International Atomic Energy Agency; International Organization Instituto Nacional de Investigaciones Nucleares; Mexico, SIM Laboratorio Nacional de Metrologia das Radiaçoes Ionizantes, IRD; Brazil, SIM Laboratorio Secundario de Calibracion Dosimetrica; Venezuela (Bolivarian Republic of), SIM National Institute of Standards and Technology; United States, SIM National Research Council; Canada, SIM *laboratory holds primary standard to allow link to the BIPM

39 SIM.RI(I)-K4 Cylindrical A12 Ionization chamber NIST and NRC standards based on water calorimeter; BIPM based on graphite (to which the secondary labs are traceable) BIPM absorbed-dose-to-water value taken as the KCRV Details in Metrologia, 2008, 45, Tech. Suppl., 06011

40 Comparisons in Radioactivity Traceability for the Radiopharmacy Currently, 128 comparisons in measurement of radionuclides (radioactivity) are listed in the Key Comparison Database Comparisons include SIM, EURAMET, COOMET, APMP, CCRI(II), BIPM (including TI) Planned, in progress, measurements complete, Draft B, approved/published, equivalence A variety of radionuclides for health, security, environmental protection, metrology; single and multiple Many matrices (from solution to soils)

41 Radionuclide Measurement Method Matrix Categorized by Radiation-type Primary measurement method Degree of difficulty color-coded CMC support by comparisons results In general, results using one primary method can not support claims (for the same nuclide) by another method Secondary methods not grouped Uncertainties are NOT benchmarks, but are reasonable to expect (for CMC reviewers aid) Rationale Radioactivity CMCs are nuclide specific Currently in excess of 1000 different combinations (quantity/nuclide/matrix) in CMCs Comparison results (quantity/nuclide/matrix) valid for limited time (eventually will be 10 years) Need to cover more than 1 quantity/nuclide/matrix with each comparison Primary methods of radionuclide metrology can be grouped according to nuclide characteristics and behavior In principal, one comparison could support dozens of CMCs at a time

42 Comparisons in Neutrons Currently, 28 comparisons in neutron measurements (fluence, fluence rate, emission rate, ambient dose and survey meter) are listed in the Key Comparison Database (KCDB; Appendix B) Comparisons include SIM, EURAMET, COOMET, APMP, CCRI(II), BIPM; generally fewer labs Planned, in progress, measurements complete, Draft B, approved/published, equivalence A variety of neutron energies reflecting various applications

43 Neutron Comparisons Comparison Topic Energy Year Status CCRI(III)-K1 Neutron fluence 24.5 kev 1993 to 1996 Valid until K11 is published CCRI(III)-K2 series Neutron fluence MeV 1983 to1986 Superseded by K10 CCRI(III)-K3 series Neutron fluence MeV 1973 to 1978 Superseded by K10 CCRI(III)-K4 series Neutron fluence MeV 1973 to 1986 Valid until 2013 CCRI(III)-K5 series Neutron fluence 2.5 MeV 1973 to 1988 Valid until K11 is published CCRI(III)-K6 series Neutron fluence 5.0 MeV 1981 to 1988 Superseded by K10 CCRI(III)-K7 series Neutron fluence 14.8 MeV 1973 to 1988 Superseded by K10 CCRI(III)-K8 Neutron fluence Thermal neutrons 2005 to 2008 Valid (replaces K8.Au) CCRI(III)-K9.AmBe Emission rate AmBe source 1999 to 2005 Valid (replaces K9.Cf-252) CCRI(III)-K10 Neutron fluence MeV, 1.2 MeV, 5.0 MeV, 14.8 MeV CCRI(III)-K11 Neutron fluence 27.4 kev 565 kev 2.5 MeV 17 MeV 2001 Valid until K11 is published 2012 Valid once published

44 CCRI(III)-K9.AmBe Participants Measurement of neutron source emission rate International comparisons are staged infrequently and take many years to perform The emission rate of an 241 Am-Be(α,n) source was measured by 8 participants Key comparison CIAE CMI KRISS China Institute of Atomic Energy; China, APMP Czech Metrology Institute; Czech Republic, EURAMET Korea Research Institute of Standards and Science; Republic of Korea, APMP LNE-LNHB Commissariat à l'énergie atomique / Laboratoire National Henri Becquerel; France, EURAMET LNMRI NIST NPL VNIIM Laboratorio Nacional de Metrologia das Radiaçoes Ionizantes, IRD; Brazil, SIM National Institute of Standards and Technology; United States, SIM National Physical Laboratory; United Kingdom, EURAMET D.I. Mendeleyev Institute for Metrology, Rostekhregulirovaniye of Russia; Russian Federation, COOMET

45 CCRI(III)-K9.AmBe Manganese bath technique to measure the neutron emission rate All (except NIST) calibrate baths with calibrated solutions of activated MnSO 4 NIST compares unknown sources to a standard Ra-Be photo-neutron source NBS-1 (stable emission rate previously measured) Results of CIAE and LNE-LNHB were not included in the KCRV (considered outliers), but later found errors (correction brought into agreement with the KCRV) Today the leading source of uncertainty comes from energy-dependent cross section uncertainties for certain key fast neutron reactions (e.g., 16 O(n,α)) NIST Mn bath Details in Metrologia, 2011, 48, Tech. Suppl., 06018

46 CCRI(III)-K11 Measurement of Neutron Fluence Comparison results valid for 10 years, remain in KCDB up to 15 years 5 NMIs able to host neutron beam comparisons Neutron energy: 27.4 kev, 565 kev, 2.5 MeV and 17 MeV Still in progress CIAE IRMM LNE-IRSN* LNMRI/IRD NIST NMIJ NPL PTB VNIIM Participants China Institute of Atomic Energy; China, APMP Institute for Reference Materials and Measurements European Union, EURAMET Institut de Radioprotection et de Sûreté Nucléaire France, EURAMET Laboratorio Nacional de Metrologia das Radiaçoes Ionizantes, IRD; Brazil, SIM National Institute of Standards and Technology; United States, SIM National Metrology Institute of Japan Japan, APMP National Physical Laboratory; United Kingdom, EURAMET Physikalisch-Technische Bundesanstalt Germany, EURAMET D.I. Mendeleyev Institute for Metrology, Rostekhregulirovaniye of Russia; Russian Federation, COOMET

47 Neutron Comparisons: CCRI(III)-K11 From Summary to CGPM Work performed by Section III Status 10-year comparison Single-centre s beams Multiple participation over 8 weeks Germany, Russia, EU- JRC, Japan, UK, USA, China Conclusions Planned update to replace 8 previous comparisons (including K10) K10 in 2001 at the PTB, Braunschweig K11 in 2011 at the LNE- IRSN, Cadarache - 10 participants 4 beam energies 4 beam energies 20 October 2011 Report to CGPM 24 47

48 Ionizing Radiation Metrology at NIST Radiation Physics (Radiation-interaction cross sections; Monte Carlo code development; Quantum metrology) Radiation Dosimetry (Brachytherapy; Mammography; Radiation processing (high dose); Worker protection) Medical Physics and Nuclear Medicine (Diagnostic; Therapeutic; Quantitative Medical Imaging) Decontamination (Industrial processing; Mail irradiation (anthrax); Luggage decon) Fundamental Neutron Physics (Weak nuclear interactions; Neutron lifetime; Neutron fluence; Calibrations) Neutron Science and Applications (Imaging; Interferometry) Radionuclide Metrology (Radionuclide standardization; SRMs; Calibrations) Environmental Radiometrology (Radiochemistry; protocols; Natural matrices; Bioassay; Environmental stewardship for nuclear power) Homeland Security (Measurements/standards for x-ray screening; Fast neutron spectrometry; Standards for radioactivity and neutron detection; Calibrated test sources; Validation testing; Evaluation Protocols; Guidance to DHS)

49 Finally Measurement traceability enables international trade World-wide metrology supports legal and regulatory aims Mutual Recognition and Equivalency allow comparability within stated uncertainties Comparisons provide basis of analysis and confidence to customers International approach brings robustness and validity to measurements NMI/DI secondary secondary Stakeholders